Process for producing 17-hydroxy-20-keto-21-acyloxy pregnanes



Patented May 13, 1952 UfNlE-TETD 'Johnl'Pat'akiyMexico City, Mexico, assignbrsto.

Syntex SaA Mexico City, Mexico, a corporaag PATENT OFFICE -tion-of-Mexico *Ne "Drawing. ApplicationOctober e0, 1950,

Serial No. 193 22 'Y-Glaims. (Cl. 260-397r4) 1 2 The present invention relates to a processfor or a radical easily convertible to preparing -cyclopentanophenantlirene deriva- H tives. 1' r More particularly the-presentinvention relates C to aprocess for the production of 1-7o li yd'rdxy- 5 6H on --k -2- t as George Rosenkranz andJohn Pataki, -Serial No. '?P topregtmne demvatwes m ad- 140151, m Ja'nugfyfl23 95 a process, dition to the var ance set fortlrm the above s'cribed for 'the 'production or -l7a-'hydroxy'20- i im convemmml; group keto-21-acy1oxy allopregnane derivatives. rmg C the cyclopentanophenanthmne As-pointed outin the aforementioned applicaexample a or group tion, the introduction of the 2l-acetoxy "group .posltlon or T above compounds into the 17-hydroxy allopregnane compounds Whlch may be charactenzed hydroxy'go' was a diflicult problem. As further pointed out keto'z'l'hailogen pregnane dgnvatlves can in the prior application, -'others had attempted cnviirted the cn7eisppdmg zlacylates by unsuccessfully to convert the bromine atom into riactmg correspondmg 217121101110 compound an acetoxy group in zbbromo auopregnane with an excess of an alkali metal salt of a lower 3,6,17p-diol-20-one 3,17-diacetate by reacting faftty acldi Prefe.mb1y the compounds are first this compound with alkali or silver acetate. In 20 dlssflved a smtable gamc solvent for the accordance with our co-pending application, compotmd as for example W ketone S01- however, the surprising discovery was made that vent acetone reactltm preferably the conversion of the 21-halogen atom into an takes place P refluxmg the i acetoxy group takes place very smoothly when compound with thealkali metal lower fatty acid the l.7 hydroxy group is in the a position. 25 salt. Typical alkali metal lower fatty acid salts In accordance with the present invention it for th? reactlon are potasmm or Sodium acetate has been discovered that the 21-halogen atom potassmm or sodmm-proplonate The pregof a lla-hydroxy compound of the character de name cqmpounds3 whlch are thus rte-acted I-nay be otherwise substituted or unsubstituted 1n the scnbed can be converted i an acetoxy group ring system, for example, substituents in the ring in the normal pregnane series as well as in the ystem may cgnsist of hydroxyl, alkoxyl agyloxyl 3110 Series described in 0111 prior pp or keto groups, or the corresponding thio deriva- The compounds which may be thus converted tives and other ether groups. The 21-halogen into the corresponding 21-acetoxy compounds derivatives, which are the starting materials for may be indicated by the following general the present invention, may be readily produced formula: by brominating the corresponding pregnane compound in a conventional manner. There- CH; after the corresponding iodo derivative, for ex- CHghalogen ample, may be prepared by reacting the 21- bromo compound with an alkali metal. iodide, 0H: L such as sodium iodide.

The following specific examples serve to illusfi trate the present invention but are not intended to limit the same. I Example I x To a solution of 14.8 g. of 21-bromo-pregnan- 3p, 17a-di01-20-OI18 in 200 cc. of acetone 10 g. of H sodium iodide in 100 cc. of acetone were added. After refluxing for ten minutes the precipitated In the fot'etgomg ffolmula X15 Selected from the sodium bromide was filtered off, the filtrate congroup COIlSlS mg 0 training the 21-iodo derivative was diluted to 500 H H cc. with acetone and refluxed with g. of potassium acetate for twelve hours. The solution 9:01 CH?! 1 u was concentrated to about cc. and poured on or; into 500 cc. water. The precipitate was filtered,

washed with water, dried and crystallized from acetone ether. Yield 11.5 g. of pregnanc- 3}3,17a,21 triol 20 one 21 acetate. Melting point: 217-219 C.

Example I I After refluxing for ten minutes the solution was filtered and the filtrate containing the 21-iodo derivative refluxed with 80 g. of potassium acetate for twelve hours. The solution was concentrated to about 200 cc., diluted with 800 cc. of water and extracted with ethyl acetate, the extract washed with water, dried and evaporated. The residue was crystallized from acetone-ether. 12.7 g. of the pregnan-3a,1'7a,21-triol-11,20-dione 21-monoacetate (melting point 217-22l C.) were obtained.

Although in the above examples the ill-halogen actually reacted are indicated as the 21-iodo compounds which are obtained by reaction of the corresponding 21-bromo compounds with sodium iodide, it is to be understood that the 21-bromo compounds may be reacted under precisely similar conditions to prepare the 21-acetate or acyloxy derivatives as set forth specifically in our copending application Serial No. 140,151.

We claim:

1. A method for producing 1'7-hydroxy-20- keto-21-acyloxy pregnane compounds, which comprises reacting 21-halogen-17a-hydroXy1-20- keto pregnane compounds with an alkali metal salt of a lower fatty acid in an organic solvent for the 21-halogen-,-l'7a-hydroxy-20-keto pregnane compounds.

2. A method for producing pregnane-3B,17a,2ltriol-20-one 21-acetate, comprising reacting 21- halogen-pregnane-3p,17a-diol-20-one with an alkali metal acetate in an organic solvent for said 21-halogen-pregnane-3fi,17a-diol-20-one.

3. A method for producing pregnane-3p,17a,21- trio1-20-one 21-acetate, comprising reacting 21- bromo-pregnane 35.1% diol 20 one with an alkali metal acetate in an organic solvent for said 21-bromo-pregnane-3p,17a-diol-20-one.

4. A method for producing pregnane-3B,17a,21- triol-20 one ill-acetate, comprising reacting 21- iodo-pregnane-ms,17a-diol-20-one with an alkali metal acetate in an organic solvent for said 21- iodo-pregnane-3fi,17a-diol-20-one.

5. A method for producing pregnane-3a,17a,21

triol-lLZO-dione 2l-monoacetate comprising reacting 21-halogen-pregnane-3,17a-diol-11,20-dione with an alkali metal acetate in an organic solvent for said 21-halogenpregnane-3a,17a-diol- 11,20-dione.

6-. A method for producing pregnane-3a,17a,21- triol-11,20-dione 2l-monoacetate comprising rcacting 21-brorno-pregnane-3a,17a-diol-1l,20-dione with an alkali metal acetate in an organic solvent for said 21-bromo-pregnane-3a,1'7a-diol- 11,20-dione.

'7. A method for producing pregnane-3a,l7a,2ltriol-11,20-dione 21-monoacetate comprising reacting 21-iodo-pregnane-3a,17a-diol-11,20-dione with an alkali metal acetate in an organic solvent for said 2l-iodo-pregnane-3a,17a-diol-l1,20-dione.

STEPHEN KAUFMANN.

GEORGE ROSENKRAN Z. JOHN PATAKI.

No references cited. 

1. A METHOD FOR PRODUCING 17-HYDROXY-20KETO-21-ACYLOXY PREGNANE COMPOUNDS, WHICH COMPRISES REACTING 21-HALOGEN-17A-HYDROXYL-20KETO PREGNANE COMPOUNDS WITH AN ALKALI METAL SALT OF A LOWER FATTY ACID IN AN ORGANIC SOLVENT FOR THE 21-HALOGEN-17A-HYDROXY-20-KETO PREGNANE COMPOUNDS. 